The purposes of this project are: (a) an assessment of the short and long term biological effectiveness of the vitamin D metabolite, 1,25-dihydroxy-vitamin D3 <1,25-(OH)2-D3> and several closely related analogs, 1-alpha-hydroxy-vitamin D3, 5,6-trans-vitamin D3 and 25- hydroxy-5,6-trans-vitamin D3 in humans under normal and pathological conditions; (b) development and clinical application of steroid-binding- assays capable of measuring circulating concentrations in plasma of l,25-(OH)2-D3, 25-OH-D3, and vitamin D3, (c) a detailed biochemical study (employing intact animals, isolated, perfused kidneys, isolated kidney tubules and/or mitochondria) of the regulation at the renal level by parathyroid hormone, calcitonin, calcium, phosphate and/or cyclic-AMP of the enzymatic conversion of 25-OH-D3 to l,25-(OH)2-D3 or other metabolites. The clinical studies of 1,25-(OH)2-D3 and related analogs will minimally include measurement of intestinal calcium absorption, blood and urine chemistries, circulating concentration of vitamin D and its metabolites, and radiological and histological assessment of bone under both metabolic balance and out-patient circumstances. Only subjects who have given an informed consent will be involved in these studies; these will include (a) normal humans; humans with (b) chronic reral failure, (c) hypophosphatemic vitamin D-resistant rickets, VDRR; (d) vitamin D- dependent rickets; (e) hypoparathyroidism; (f) sarcoidosis; (g) hyperparathyroidism; or (h) idiopathic hypercalciuria; and (i) patients treated with anticonvulsants.